SEMEN ANALYSIS PARAMETERS DO NOT CHANGE DURING ACTIVE COVID INFECTION IN KNOWN SPERM DONORS

OBJECTIVE: The effects of SARS-CoV-2 were initially studied in the respiratory system, but research has now shown manifestations in multiple organ systems. SARS-CoV-2 is known to enter target cells through the ACE- 2 receptor, which is expressed in the testes. Due to this, the testes has been purported to be a potential target for SARS-CoV-2 infection. To date, studies have suggested that there is only a minor risk for shedding of SARS-CoV-2 into the semen.1 The objective of this study is to compare semen analysis parameters in a subset of healthy sperm donors prior to, during, and after testing positive for COVID-19. MATERIALSAND METHODS: The study included semen analyses (SA) from qualified sperm donors aged 19-38, with 2-5 days of abstinence who donated sperm prior to COVID infection, during active COVID infection, and post COVID infection. Semen was collected in the course of sperm bank operation and samples were collected concurrent with incidental positive test results obtained through COVID screening. Primary outcomes included ejaculate volume (mL), average concentration (M/mL), and percent motility (%). The standard operating procedure for sperm donation dictated that morphology is performed when they are first accepted into the program, thus was not recorded for these samples. Data were compared and analyzed by ANOVA. RESULTS: A total of five qualified sperm donors met inclusion criteria for this study. When comparing semen analyses across the three time points, there was not a significant difference in concentration (p=0.7460), percent motility (p=0.9135), or ejaculate volume (p=0.9241) [Table 1]. CONCLUSIONS: Sperm quality measures as evidenced in qualified, healthy sperm donors are not significantly different when comparing sperm samples prior to COVID infection, during active COVID infection, and after recovery from COVID infection. Although limited by a small sample size, our findings are reassuring to those with SARS-CoV-2 infection, as there appears to be no adverse association with sperm quality. IMPACT STATEMENT: Sperm quality in healthy, qualified donors is not affected by active SARS-CoV-2 infection.

THE NEW NORMAL: PATIENT PROGRESSION TO FERTILITY TREATMENT IN A COVID-19 WORLD

OBJECTIVE: The coronavirus (COVID-19) pandemic reshaped access to assisted reproductive technology (ART) treatment. Following ASRM's March 2020 recommendation to halt all ART treatments, many patients were unable to pursue parenthood until resumption of clinical care. Our study assesses patient progression to reproductive care before, during and after the declaration of the COVID-19 pandemic. MATERIALS AND METHODS: The study includes patients who sought ART treatment from January 1, 2018 to October 1, 2020. Only patients who underwent an initial consultation were included in the study. Patients were grouped by month in the years of 2018, 2019, and 2020. Patient progression to treatment was confirmed only if the ART procedure occurred within 90 days after initial consultation. RESULTS: A total of 27,626 initial consultations from patients who sought ART treatment were evaluated in the study. Treatment progression rates for 2018 and 2019 showed high correlation with nearly identical rates per month from March to July [Table 1]. Patient progression declined to 47.9% starting in January 2020 compared to 57.3% in 2018 and 59.4% in 2019 of the same month. Thereafter, progression to treatment dropped to an all-time low (February-March 2020 (32.0-33.0%)). Progression rate increased by late April 2020 (47.7%);and then surged in May 2020 (55.7%) superseding treatment progression rates between the same months during 2018 (47.4%) & 2019 (47.9%). By the end of August and throughout September 2020 progression to treatment restored itself to rates in 2018 & 2019 [Table 1]. CONCLUSIONS: As compared to cohorts in 2018 and 2019, our study demonstrated a marked decline in progression to ART treatment that coincided with the onset of the COVID pandemic and when many regions of the country restricted all but urgent medical procedures. As COVID-related restrictions lifted, treatment progression rates sharply rebounded and then stabilized by September 2020. The recovery to treatment progression displays fertility care as essential to patients and reaffirms a strong desire to have children. IMPACT STATEMENT: The barriers related to the onset of the COVID pandemic were short-lived for patients who sought ART treatment. Even with COVID's introduction of new normal, patients can be reassured that they have the ability to access reproductive care and achieve parenthood.

REVISITING OLD HABITS: THERE IS NO BENEFIT IN PRESCRIBING METHYLPREDNISOLONE ADMINISTRATION DURING EUPLOID EMBRYO TRANSFERS IN THE GENERAL INFERTILE POPULATION

OBJECTIVE: Two decades ago, a small RCT concluded that embryos with an incision in the zona pellucida could be protected from an immune response by administering systemic corticosteroids1. The utilization of corticosteroids remains a standard practice at many ART centers 2,3. In early 2020, during the peak of the Sars-Cov-2 pandemic, some reports showed that corticosteroid intake associated with an extended time of viral shedding which associated to higher mortality among patients with coronavirus pneumonia4. Our center therefore discontinued standard of methylprednisolone in frozen embryo transfer (FET) cycles. Our study aims to evaluate IVF pregnancy outcomes of patients who underwent a short course of oral steroids compared to those that were not treated with corticosteroids. MATERIALS AND METHODS: All patients who underwent IVF from 2016 - 2021 were included. All cases underwent PGT-A with NGS. Only patients who underwent a single euploid FET under a synthetic endometrial preparation cycle were included. Cohorts were separated by use of steroids prior to ET (Group A: Oral methylprednisolone Treatment (16mg for 7 days);Group B: non-treatment controls). Patients with RPL, implantation failure and uterine factor were excluded. Baseline, demographic characteristics and cycle outcomes were recorded. Comparative statistics and a multivariate regression analysis fitted with a GEE were utilized for statistical analysis. A sample size of 1,437 FET's per group was calculated to have an 80% power to detect a difference of 5% on implantation rates, a=0.05. RESULTS: A total of 7,172 cycles were included in the analysis, 5,002 cycles with methylprednisolone utilization were compared against 2,170 controls. No differences were found in oocyte age, age at FET, BMI, AMH, FSH, previous cycles, days of endometrial preparation, endometrial thickness at FET and embryo quality at FET among cohorts. When comparing IVF outcomes, in an unadjusted-analysis a difference was found in implantation rates among patients that used methylprednisolone compared with controls (75.8% vs 72.8%, p=0.008), clinical pregnancy, ongoing pregnancy and clinical pregnancy loss rates were comparable among groups. In a multivariate analysis after adjusting for oocyte age, day of biopsy, embryo quality, BMI, AMH, and endometrial thickness at ET, no association was found with the utilization of Methylprednisolone and higher implantation (OR 1.1 CI95% 0.9-1.2), clinical pregnancy (OR1.02;0.9-1.1), ongoing pregnancy (OR 0.9;0.8-1.08) or higher odds of clinical pregnancy loss (OR 1.1;0.9-1.4) CONCLUSIONS: Systemic corticosteroids use continues to be a controversial, yet widespread, adjuvant treatment during IVF cycles in many modern ART centers. Our study demonstrated the utilization of methylprednisolone is not associated with increased odds of implantation, ongoing pregnancy or decreased odds of pregnancy loss after a single euploid FET. IMPACT STATEMENT: Our findings add to the growing body of evidence suggesting that the standard use of peri-implantation corticosteroids does not enhance nor impact reproductive outcomes in FET cycles.

SIXTEEN YEAR LONGITUDINAL STUDY OF U.S. SPERM DONORS CONTINUES TO DEMONSTRATE DECLINING SPERM COUNT AND MOTILITY

OBJECTIVE: It has been suggested that geographic variations in environmental toxins may impact sperm quality. Previously, we published findings that demonstrated a decline in sperm quality over an eleven year period across six regions of the United States (US).1 The current study investigates whether there was a decrease in sperm quality from a diverse set of US sperm donors across six regions in the US over a sixteen year period. Additionally, this study sought to evaluate changes between semen analysis (SA) parameters in an era of sperm collection during the COVID-19 pandemic. MATERIALS AND METHODS: Semen analyses (SA) from sperm donors aged 19-38, with 2-5 days abstinence, from 9 different geographic regions from January 2005-April 2021 were examined. The sperm donors originated from one of the following regions: Palo Alto, Los Angeles, Westwood, International Nordic Cryo Bank Denmark, Indianapolis, Cambridge, New York, Houston, and Spokane, WA. Donation date, BMI, and geographic region were recorded. Data was analyzed as a whole as well as by individual region. Primary outcomes were ejaculate volume (mL), average concentration (M/mL), motility (%), and total motile count (M). Data was analyzed using a general estimate equation (GEE) model with an exchangeable working correlation structure to account for repeated measures. RESULTS: A total of 176,706 SA specimens (from 3,532 unique donors) were analyzed. Controlling for BMI, there was a significant decline in average concentration (M/mL) (β=-1.89, p<0.0001), sperm motility (%) (β=-0.2892, p<0.0001) and total motile sperm (M) (β=-4.53, p<0.0001) over the 16-year study period. There were significant decreases in SA parameters within all geographic regions (Spokane only had two unique donors and could not be examined). Indianapolis showed a significant decrease in sperm concentration and total motile sperm, but also displayed an increase in sperm motility over the study period. CONCLUSIONS: Time related decline in sperm quality continues to be evident at a national level in young, healthy sperm donors. There was a decline across all geographic regions in all parameters except for ejaculate volume. How this decline in sperm counts impacts fertility has yet to be determined. Our modern environment involves increased exposures to endocrine disruptors and changes to lifestyle (including smoking, diet, and stress) that are postulated to impair male fertility by interfering with spermatogenesis. While a causative link to these risk factors remains to be elucidated further studies are necessary to evaluate whether this temporal decline in sperm count correlates with decreased fecundity. IMPACT STATEMENT: Sperm concentration, motility, and total motile sperm continue to decline across young, healthy sperm donors across the continental United States.

MRNA COVID-19 VACCINES DO NOT COMPROMISE IMPLANTATION OF EUPLOID EMBRYOS

OBJECTIVE: Concerns have arisen in the lay press regarding a theoretical impact of the COVID-19 vaccine on fertility and early pregnancy. These concerns originate from speculation regarding homology between the COVID- 19 spike protein targeted by the vaccine and syncitin-1 protein, which mediates cytotrophoblast and syncytiotrophoblast fusion and placental development. 1 While this theory has been deconstructed by immunology experts, robust clinical studies have yet to examine a relationship between the mRNA COVID-19 vaccines and reproductive potential. This study aims to assess whether COVID-19 vaccination status impacts early pregnancy outcomes in patients undergoing IVF. MATERIALS AND METHODS: This study included patients who underwent single euploid frozen-thawed embryo transfer (FET) at a single academic center. Vaccinated patients who received the second dose of the Pfizer or Moderna mRNA vaccine two weeks prior to single euploid FET were compared to non-vaccinated patients who underwent single euploid FET during the same time period. Patients who received vaccine doses less than 14 days prior to FET were excluded. Outcomes included pregnancy rate (HCG R2.5IU/L), clinical pregnancy rate (presence of a gestational sac on ultrasound), ongoing pregnancy rate, and pregnancy loss rate. Statistical analysis was performed using Chi-square, Student's t-test, and multivariable logistic regression to control for confounders. RESULTS: Of the 65 patients who underwent single euploid FET two weeks after their final vaccine dose, 28 patients received the Pfizer vaccine and 37 received the Moderna vaccine. Fully vaccinated patients underwent FET between February-April 2021. During that time period 328 non-vaccinated patients underwent single euploid FET and comprised the control group. Baseline characteristics including age, oocyte age, BMI, AMH, BAFC, and endometrial thickness were similar between the groups. Vaccinated and non-vaccinated patients had similar pregnancy rates (75.6% vs. 73.0%, p=.72) and clinical pregnancy rates (63.4% vs. 56.9%, p=.43). No significant differences were seen in pregnancy loss rates (11.8% vs. 23.2%, p=.13) or ongoing pregnancy rates (66.7% vs. 56.1%, p=.18) between the groups. Controlling for age, BMI, AMH, and endometrial thickness revealed no association between vaccination and early pregnancy outcomes (Pregnancy: aOR 1.15, 95% CI 0.49- 2.75, p=.75;Clinical pregnancy: aOR 1.42, 95% CI 0.65-3.10, p=.38;Ongoing pregnancy: aOR 1.67, 95% CI 0.77-3.61, p=.19;Pregnancy loss: aOR 0.39, 95% CI 0.11-1.37, p=.14). CONCLUSIONS: Administration of COVID-19 mRNAvaccines does not interfere with early pregnancy in patients who undergo transfer of genetically screened embryos. There is no relationship between immune response to the COVID-19 spike protein and placental development. IMPACT STATEMENT: Patients who are planning pregnancy can be reassured that COVID-19 vaccination does not adversely impact early pregnancy outcomes. Our findings serve to debunk circulating myths and substantiate that the risk/benefit ratio supports vaccination in women who are trying to conceive.

UNDERSTANDING THE PATIENT EXPERIENCE IN THE DIGITAL AGE: VIRTUAL MEDICINE AND PATIENT PROGRESSION TO FERTILITY TREATMENT

Objective: Fertility practices have been profoundly impacted by the global COVID-19 pandemic, leading to a rapid increase in the utilization of new forms of virtual communication with patients. This study aimed to assess the use of telemedicine compared to conventional in-person consultation with regard to the rate of patient progression to treatment. Materials and Methods: The study included patients who sought reproductive treatment and underwent an initial consultation during from March 2, 2020 to December 22, 2020. Patients were grouped by in person or telemedicine at initial consultation. Patients who met in person underwent a physical exam and ultrasound the same day as the initial consultation. Patients who met via telemedicine were contacted after the initial consultation to schedule a physical exam and ultrasound at a later date. All patients were followed up with by a clinical team member and financial coordinator either in person or virtually following initial consultation. Study outcomes included number of patients who progressed to treatment. Secondary outcome included time to treatment. Treatment was defined as a patient who underwent a diagnostic procedure, surgical procedure, timed intercourse cycle, intrauterine insemination cycle, in vitro fertilization cycle, egg freezing cycle, laboratory procedure, or embryo transfer cycle. A 90 day censoring interval was applied to account for heterogeneity between initial consultation date and progression to treatment event. Results: Of the 2730 patients included in the study, 2153 (79.9%) received in person consultation and 550 (20.1%) communicated via telemedicine. The percentage of patients who progressed to treatment within 90 days of initial consultation was nearly identical between in person (35.4 %) and telemedicine patients (34.0 %). Patients who underwent in person consultation advanced to treatment 3 days faster (41.1 days) compared to telemedicine patients (44.0 days) within the 90 day censoring interval [Table 1]. [Formula presented] Conclusions: The COVID-19 pandemic has forever changed society, healthcare, and reproductive medicine. While infertility patients who utilize telemedicine for initial consultation take longer to initiate treatment, they are equally likely to enter treatment. Impact Statement: Use of telemedicine breaks down barriers to treatment and provides the opportunity for patients everywhere to access reproductive care in their journey to parenthood.

PREGNANCY LOSS RATES AFTER SINGLE, EUPLOID FROZEN-THAWED EMBRYO TRANSFER IN THE COVID-19 ERA

Objective: Data on the impact of COVID-19 on early pregnancy is extremely limited, and patients and practitioners remain cautious about initiating pregnancy in areas of high SARS-CoV-2 transmission.1-4 In April 2020, during the peak of the pandemic, the prevalence of COVID-19 among New York State residents was estimated to be 22.7%, consisting largely of asymptomatic infection.5 If SARS-CoV-2 is pathogenic to early pregnancy, an increase in loss might be expected given this high transmission. The objective of this study is to determine if an increase in early pregnancy loss occurred in patients undergoing single euploid frozen embryo transfer (FET) during the height of the COVID-19 pandemic. Design: Retrospective cohort study. Materials and Methods: The study took place at an academic tertiary care center with offices throughout New York City. All single euploid FET cycles performed from January-May of 2017-2020 were included. Cycles with FET in 2017-2019 were compared to those with FET performed in the corresponding time period in 2020. Baseline characteristics included age, oocyte age, AMH, BMI, and endometrial thickness. Pregnancy loss rate (PLR), or loss after the presence of serum βhCG ≥2.5 mIU/mL, and clinical pregnancy loss rate (CLR), loss after a gestational sac was seen on ultrasound, were compared between January-May, 2017-2019 and January-May, 2020, in aggregate as well as for each corresponding month individually. Comparative statistics and multivariable logistic regression were used. Results: 2629 single euploid FET cycles were included in the study: 2070 from Jan-May, 2017-2019 and 559 from Jan-May, 2020. Positive pregnancy rates were 73.7% in January-May, 2017-2019 and 77.6% in January-May, 2020. Baseline characteristics were similar. No differences were seen in PLR or CLR when comparing FET from January-May, 2017-2019 to FET from January-May, 2020. No differences were seen in PLR or CLR when comparing individual months in 2017-2019 to 2020. On multivariable logistic regression, when controlling for oocyte age, AMH, BMI, and endometrial thickness, FET in January-May 2017-2019 was associated with a higher odds of pregnancy loss compared to January-May 2020 (OR 1.32, 95% CI 1.02-1.73, p=.039). No difference was seen in CLR between these groups (OR 1.34, 95% CI 0.92-1.97, p=.13). No differences were seen in PLR or CLR comparing each month individually in the two time periods. Conclusions: This data is reassuring that early pregnancy loss rates were not increased during widespread SARS-CoV-2 transmission. A decrease in PLR in January-May 2020 compared to prior years might be attributable to selection against treatment of patients with known risk factors for severe infection. While in the absence of universal screening for SARS-CoV-2, which at the time was neither available nor recommended, this data does not exclude a possible impact of infection on pregnancy loss, it suggests that screening patients for elevated temperature, symptoms, and exposure may be effective in maintaining established early pregnancy success rates. This data may help guide clinics in regions experiencing a surge in virus transmission. SUPPORT: None References: 1. Kasraeian M, Zare M, Vafaei H, et al. COVID-19 pneumonia and pregnancy;a systematic review and meta-analysis [published online ahead of print, 2020 May 19]. J Matern Fetal Neonatal Med. 2020;1-8. 2. Knight M, Bunch K, Vousden N, et al. Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study. BMJ. 2020;369:m2107. Published 2020 Jun 8. 3. Galang RR, Chang K, Strid P, et al. Severe Coronavirus Infections in Pregnancy: A Systematic Review [published online ahead of print, 2020 Jun 16]. Obstet Gynecol. 2020;10.1097/AOG.0000000000004011. 4. ASRM Patient management and Clinical Recommendations During the Coronavirus (COVID-19) Pandemic Update #6 (7/10/2020-8/10/2020) 5. Rosenberg ES, Tesoriero JM, Rosenthal EM, et al. Cumulative incidence and diagnosis of SARS-CoV-2 infection in Ne York [published online ahead of print, 2020 Jun 17]. Ann Epidemiol. 2020;S1047-2797(20)30201-5.

IVF TREATMENT PRE- AND POST- THE ASRM COVID-19 PAUSE

Objective: The coronavirus (COVID-19) pandemic has forever reshaped the United States health care system. However, assisted reproductive technology (ART) treatment remains an essential form of medicine. Reproductive practices have since incorporated vigilant practices regarding social distancing, ample use of Personal Protective Equipment (PPE), and consistent decontamination protocols in order to mitigate risk of COVID-19 infection. Altogether, changes to standard operating procedures within ART treatment centers are anticipated to support patient safety without compromising quality of reproductive care. Finally, there is ample evidence of the mental health burden stemming from this pandemic with regard to anxiety and depression in both healthcare workers and patients. Given the current uncertainty, our study evaluates IVF cycle outcome in a New York City patient cohort prior to and subsequent to the ASRM COVID-19 task force’s recommended treatment pause. Design: Retrospective cohort analysis. Materials and Methods: The study includes patients who underwent a single, euploid frozen-thawed embryo transfer (FET) from January 1st, 2020 to May 18th, 2020. Cohorts were separated into two groups based on period of IVF treatment (Group 1: Treatment prior to the COVID-19 pandemic pause;Group 2: Treatment subsequent to the COVID-19 pause). Primary outcome included early pregnancy rates. Chi squared test was used and statistically significance was considered at p= <0.05. Results: A total of 601 single, euploid FET cycles in which pregnancy outcomes coming prior to the COVID-19 pandemic pause (n=526) were compared to outcomes subsequent to COVID-19 (n=75). No differences were found in early pregnancy rates among cohorts (Table 1). [Formula presented] Conclusions: The COVID-19 pandemic has placed an unprecedented burden on patients, physicians, and the entire healthcare system. Urgent treatments, including reproductive care, were postponed, as scarce resources needed to be re-directed. Resumption of treatment required modification in workflow, staffing, decontamination protocols, and utilization of PPE. Although the patient experience has changed, our study is first to demonstrate implantation rates were not compromised in an era of COVID-19. Importantly, our preliminary data suggests that the stress and anxiety that pervade modern COVID-era reproductive care do not alter outcomes. With an abundance of caution, a modern fertility clinic can work to “flatten the curve,” abide by guidelines, and deliver safe and effective patient care.